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Prenatal diagnosis of glutaric acidemia type 2 with the use of exome sequencing — an up-to-date review and new case report
, 1, 2, 2, 3, 1, 1, 1, 4, 2
Affiliations- Department of Gynecology Oncology and Obstetrics, Centre of Postgraduate Medical Education, Warsaw, Poland
- Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland
- Second Department of Obstetrics and Gynecology, Centre of Postgraduate Medical Education, Warsaw, Poland
- Department of Pathology, Professor Witold Orlowski Public Clinical Hospital, Medical Center for Postgraduate Education, Warsaw, Poland
open access
Abstract
Introduction: Inborn errors of metabolism (IEM) also called metabolic diseases constitute a large and heterogenous group of disorders characterized by a failure of essential cellular functions. Antenatal manifestation of IEM is absent or nonspecific, which makes prenatal diagnosis challenging. Glutaric acidemia type 2 (GA2) is a rare metabolic disease clinically manifested in three different ways: neonatal-onset with congenital anomalies, neonatal-onset without congenital anomalies and late-onset. Neonatal forms are usually lethal. Congenital anomalies present on prenatal ultrasound as large, hyperechoic or cystic kidneys with reduced amniotic fluid volume. Material and methods: We present a systematic literature review describing prenatal diagnosis of GA2 and a new prenatal case. Results: Ten prenatally diagnosed cases of GA2 have been published to date, mainly based on biochemical methods. New case of GA2 was diagnosed using exome sequencing method. Discussion: All prenatal cases from literature review had positive history of GA2 running in the family. In our study trio exome sequencing was performed in case of fetal hyperechoic kidneys without a history of GA2. Consequently, we were able to identify two novel pathogenic variants of the ETFDH gene and to indicate their parental origin. Summary: Exome sequencing approach used in case of fetal hyperechoic kidneys allows to identify pathogenic variants without earlier knowledge of the precise genetic background of the disease. Hyperechoic, enlarged kidneys could be one of the clinical features of metabolic diseases. After exclusion of chromosomal abnormalities, urinary tract obstruction and intrauterine infections, glutaric acidemia type 2 and number of monogenic disorders should be consider.
Abstract
Introduction: Inborn errors of metabolism (IEM) also called metabolic diseases constitute a large and heterogenous group of disorders characterized by a failure of essential cellular functions. Antenatal manifestation of IEM is absent or nonspecific, which makes prenatal diagnosis challenging. Glutaric acidemia type 2 (GA2) is a rare metabolic disease clinically manifested in three different ways: neonatal-onset with congenital anomalies, neonatal-onset without congenital anomalies and late-onset. Neonatal forms are usually lethal. Congenital anomalies present on prenatal ultrasound as large, hyperechoic or cystic kidneys with reduced amniotic fluid volume. Material and methods: We present a systematic literature review describing prenatal diagnosis of GA2 and a new prenatal case. Results: Ten prenatally diagnosed cases of GA2 have been published to date, mainly based on biochemical methods. New case of GA2 was diagnosed using exome sequencing method. Discussion: All prenatal cases from literature review had positive history of GA2 running in the family. In our study trio exome sequencing was performed in case of fetal hyperechoic kidneys without a history of GA2. Consequently, we were able to identify two novel pathogenic variants of the ETFDH gene and to indicate their parental origin. Summary: Exome sequencing approach used in case of fetal hyperechoic kidneys allows to identify pathogenic variants without earlier knowledge of the precise genetic background of the disease. Hyperechoic, enlarged kidneys could be one of the clinical features of metabolic diseases. After exclusion of chromosomal abnormalities, urinary tract obstruction and intrauterine infections, glutaric acidemia type 2 and number of monogenic disorders should be consider.
Keywords
inborn errors of metabolism; glutaric acidemia type 2; multiple acyl-coenzyme A dehydrogenase deficiency; fetal abnormalities; prenatal diagnosis; exome sequencing
About this articleTitle
Prenatal diagnosis of glutaric acidemia type 2 with the use of exome sequencing — an up-to-date review and new case report
Journal
Issue
Article type
Review paper
Pages
51-56
Published online
2020-12-30
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1421
Article views/downloads
1384
DOI
Pubmed
Bibliographic record
Ginekol Pol 2021;92(1):51-56.
Keywords
inborn errors of metabolism
glutaric acidemia type 2
multiple acyl-coenzyme A dehydrogenase deficiency
fetal abnormalities
prenatal diagnosis
exome sequencing
Authors
Anna M. Kucinska-Chahwan
Tomasz Roszkowski
Maciej Geremek
Magdalena A. Paczkowska
Michal Ciebiera
Julia Bijok
Diana Massalska
Grzegorz Panek
Krzysztof Siemion
Beata A. Nowakowska
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